This project extends a long line of mental retardation research within this Program Project on the behavioral phenotypes of various genetic syndromes. Specifically, this Project measures the development of psychopathology and psychosocial, genetic, and familial features in Prader-Willi, Williams and Down syndromes, and in a comparison group. these features are examined in a longitudinal-sequential study with placebo-controlled pharmacotherapy studies. We select Prader-Willi, Williams and Down syndromes for study because of their novel relations to other disorders in this Program Project; their molecular genetic characteristics and promise for gene-behavior understandings; and their compelling clinical features. There are three, overarching hypotheses in this project: (1) syndromic status predisposes persons with mental retardation to particular types of psychopathology and to distinctive shifts in these features over the course of development; (2) within-syndrome variability in the expression of psychopathology is likely associated with molecular genetic features as well as with psychosocial, developmental, and familial factors derived from well-established models of dual diagnosis; and (3) pharmacotherapy using serotonin-uptake inhibitors can alleviate symptom expression of psychopathology associated with Prader-Willi syndrome, including obsessive, compulsive and affective features. Findings will integrate the behavioral and biological approaches to research in mental retardation; advance knowledge of genotype-phenotype relations; and pave the way for novel behavioral and pharmacologic interventions that are based on syndrome-specific strengths, weaknesses and developmental trajectories.